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Nalidixic acid

First of the synthetic quinolone antibiotics

Field	Value
Watchedfields	changed
verifiedrevid	462258277
IUPAC_name	1-Ethyl-7-methyl-4-oxo-[1,8]naphthyridine-3-carboxylic acid
image	Nalidixic Acid Structure.svg
image_class	skin-invert-image
tradename	NegGram, Wintomylon, others
Drugs.com
pregnancy_US	B
legal_US	Not FDA approved
routes_of_administration	Oral
protein_bound	90%
metabolism	Partially Hepatic
elimination_half-life	6-7 hours, significantly longer in renal impairment
CAS_number_Ref
CAS_number	389-08-2
ATC_prefix	J01
ATC_suffix	MB02
PubChem	4421
DrugBank_Ref
DrugBank	DB00779
ChemSpiderID_Ref
ChemSpiderID	4268
UNII_Ref
UNII	3B91HWA56M
KEGG_Ref
KEGG	D00183
ChEBI_Ref
ChEBI	100147
ChEMBL_Ref
ChEMBL	5
C	12	H=12	N=2	O=3
smiles	O=C\2c1c(nc(cc1)C)N(/C=C/2C(=O)O)CC
StdInChI_Ref
StdInChI	1S/C12H12N2O3/c1-3-14-6-9(12(16)17)10(15)8-5-4-7(2)13-11(8)14/h4-6H,3H2,1-2H3,(H,16,17)
StdInChIKey_Ref
StdInChIKey	MHWLWQUZZRMNGJ-UHFFFAOYSA-N

| Drugs.com = | elimination_half-life = 6-7 hours, significantly longer in renal impairment

Nalidixic acid (tradenames Nevigramon, NegGram, Wintomylon and WIN 18,320) is the first of the synthetic quinolone antibiotics.

In a technical sense, it is a naphthyridone, not a quinolone: its ring structure is a 1,8-naphthyridine nucleus that contains two nitrogen atoms, unlike quinoline, which has a single nitrogen atom.

Synthetic quinolone antibiotics were discovered by George Lesher and coworkers as a byproduct of chloroquine manufacture in the 1960s; nalidixic acid itself was used clinically, starting in 1967.

Nalidixic acid is effective primarily against Gram-negative bacteria, with minor anti-Gram-positive activity. In lower concentrations, it acts in a bacteriostatic manner; that is, it inhibits growth and reproduction. In higher concentrations, it is bactericidal, meaning that it kills bacteria instead of merely inhibiting their growth.

It has historically been used for treating urinary tract infections, caused, for example, by Escherichia coli, Proteus, Shigella, Enterobacter, and Klebsiella. It is no longer clinically used for this indication in the US as less toxic and more effective agents are available. The marketing authorization for nalidixic acid has been suspended throughout the EU.

It is also a tool in studies as a regulation of bacterial division. It selectively and reversibly blocks DNA replication in susceptible bacteria. Nalidixic acid and related antibiotics inhibit a subunit of DNA gyrase and topoisomerase IV and induce formation of cleavage complexes. It also inhibits the nicking-closing activity on the subunit of DNA gyrase that releases the positive binding stress on the supercoiled DNA.

Adverse effects

Hives, rash, intense itching, or fainting soon after a dose may be a sign of anaphylaxis. Common adverse effects include rash, itchy skin, blurred or double vision, halos around lights, changes in color vision, nausea, vomiting, and diarrhea. Nalidixic acid may also cause convulsions and hyperglycemia, photosensitivity reactions, and sometimes hemolytic anemia, thrombocytopenia or leukopenia. Particularly in infants and young children, has been reported occasionally increased intracranial pressure.

Overdose

In case of overdose the patient experiences headache, visual disturbances, balance disorders, mental confusion, metabolic acidosis and seizures.

Spectrum of bacterial susceptibility and resistance

Aeromonas hydrophila, Clostridium and Haemophilus are generally susceptible to nalidixic acid, while other bacteria such as Bifidobacteria, Lactobacillus, Pseudomonas and Staphylococcus are resistant. Salmonella enterica serovar Typhimurium strain ATCC14028 acquires nalidixic acid resistance when gyrB gene is mutated (strain IR715).

References

(May 2003). "The quinolones: decades of development and use". The Journal of Antimicrobial Chemotherapy.
(September 1962). "1,8-Naphthyridine Derivatives. A New Class of Chemotherapeutic Agents". Journal of Medicinal and Pharmaceutical Chemistry.
(11 March 2019). "Disabling and potentially permanent side effects lead to suspension or restrictions of quinolone and fluoroquinolone antibiotics".
(May 2010). "DNA topoisomerases and their poisoning by anticancer and antibacterial drugs". Chemistry & Biology.
(December 1977). "Convulsions and hyperglycaemia associated with nalidixic acid". British Medical Journal.
(August 1973). "Photosensitivity from nalidixic acid". Proceedings of the Royal Society of Medicine.
(November 1972). "Haemolytic anaemia with nalidixic acid". British Medical Journal.
(October 1982). "Fatal acute immune haemolytic anaemia caused by nalidixic acid". British Medical Journal.
(October 1984). "Thrombocytopenia induced by nalidixic acid". British Medical Journal.
(June 1967). "Intracranial hypertension in a child during treatment with nalidixic acid". British Medical Journal.
(November 1967). "Nalidixic acid and intracranial hypertension". British Medical Journal.
(September 1974). "Acute intracranial hypertension after nalidixic acid administration". Archives of Disease in Childhood.
(March 2006). "Nalidixic acid overdose and metabolic acidosis". CJEM.
(2011-09-14). "Nalidixic acid spectrum of bacterial susceptibility and Resistance". Toku-E.
(March 1995). "Ethanolamine utilization in Salmonella typhimurium: nucleotide sequence, protein expression, and mutational analysis of the cchA cchB eutE eutJ eutG eutH gene cluster". Journal of Bacteriology.

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quinolone-antibiotics naphthyridines win-compounds carboxylic-acids topoisomerase-inhibitors

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